Gd-EOB-DTPA-MRI Could Predict WNT/β-Catenin Mutation and Resistance to Immune Checkpoint Inhibitor Therapy in Hepatocellular Carcinoma

• Published in: Liver cancer (Basel ) 2020-09, Vol.9 (5), p.479-490
• Main Author: Kudo, Masatoshi
• Format: Article
• Language: English
• Subjects: anti-pd-1/pd-l1; Biomarkers; Classification; Editorial; hepatocellular carcinoma; immune checkpoint inhibitor; Immunotherapy; Inhibitor drugs; Liver cancer; Lymphocytes; Magnetic resonance imaging; Medical prognosis; Monoclonal antibodies; Mutation; Targeted cancer therapy; Transcription factors; Tumors; wnt/β-catenin mutation
• ISSN: 2235-1795; 1664-5553
• DOI: 10.1159/000509554

Melanoma with WNT/β-catenin mutations is characterized by a decreased recruitment of CD103+ DCs and CD8+ T cells, and the underlying mechanism involves the induction of activating transcription factor 3 via WNT/β-catenin signaling and the consequent decrease in chemokine (c-c motif) ligand 4 (CCL4) production [16, 17] (Fig. 3). See PDF.] PFS of patients with advanced HCC treated with ICI and sorafenib This was a breakthrough that provided clinical proof, albeit in a small number of cases, of the hypothesis that HCC with WNT/β-catenin mutation/activation are immune cold tumors because of decreased tumor infiltration of CD8+ T cells and are thus resistant to ICI therapy. The PD rate was 37% with nivolumab monotherapy in the CheckMate 459 trial [20], 32.4% with pembrolizumab monotherapy in KEYNOTE 240 [21], and 20% with atezolizumab plus bevacizumab combination therapy in the IMbrave 150 trial [22]. [...]the PD rate of lenvatinib plus pembrolizumab was extremely low (7%) per RECIST 1.1 in a phase 1b study [23]. In accordance with the decrease in the relative enhancement ratio (RER), which is the ratio of the enhancement intensity in the tumor region to that in the nontumor region in the HBP of EOB-MRI, immunohistochemical staining for OATP1B3 in resected specimens showed a gradual decrease of OATP1B3 expression in correlation with multistep carcinogenesis from low-grade dysplastic nodule (DN) to high-grade DN, early HCC, well-differentiated HCC, moderately differentiated HCC, and finally poorly differentiated HCC [29].